The goal of this project is to gain an understanding of the regulation of the GnRH gene in the hypothalamus. Aim 1 is to understand the basis of neuron-specific expression of the GnRH gene. The tissue-specific actions of known proteins on the GnRH gene enhancer will be defined, and additional proteins that interact with the enhancer identified. Aim 2 is to identify the elements and target proteins important for mediating the actions of the NMDA/NO/cGMP or PKC pathways to repress transcription of the GnRH gene. Aim 3 is to develop a new GnRH cell model system using transgenic animal technologies, in which the transforming oncogene can be switched off in culture to allow the cells to become postmitotic.